Immunostimulatory compositions and methods comprising an ITIM motif-containing DC immunoreceptor (DCIR) to mediate potent crosspresentation are described herein. The inventors evaluated human CD8+ T cell responses generated by targeting antigens to dendritic cells (DCs) through various lectin receptors. A single exposure to a low dose of anti-DCIR-antigen conjugate initiated antigen-specific CD8+ T cell immunity by all human DC subsets including ex vivo generated DCs, skin-isolated Langerhans cells and blood mDCs and pDCs. Enhanced specific CD8+ T cell responses were observed when antigens like, FluMP, MART-1, viral (HIV gag), etc. were delivered to the DCs via DCIR, compared to those induced by a free antigen, or antigen conjugated to a control mAb or delivered via DC-SIGN, another lectin receptor. Addition of Toll-like receptor (TLR) 7/8-agonist enhanced DCIR-mediated crosspresentation as well as crosspriming. Thus, antigen targeting via the human DCIR receptor allows activation of specific CD8+ T cell immunity.本文闡述免疫刺激組合物及方法,其包含用於調節有效交叉呈遞之含ITIM基序之DC免疫受體(DCIR)。本發明者評估藉由經由各種凝集素受體使抗原靶向樹突狀細胞(DC)後所產生之人類CD8+ T細胞反應。單次暴露於低劑量抗DCIR-抗原偶聯物即可啟動所有人類DC亞群之抗原特異性CD8+ T細胞免疫性,該等DC亞群包括離體生成之DC、自皮膚分離之朗格漢斯(Langerhans)細胞及血液mDC及pDC。與彼等藉由游離抗原、或偶聯至對照mAb或經由另一種凝集素受體DC-SIGN遞送之抗原所誘導之反應相比,當經由DCIR將諸如FluMP、MART-1、病毒(HIV gag)等抗原遞送至DC中時,觀察到增強之特異性CD8+ T細胞反應。添加類鐸(Toll-like)受體(TLR) 7/8激動劑可增強DCIR調節之交叉呈遞以及交叉敏化作用。因此,經由人類DCIR受體之抗原靶向可以活化特異性CD8+ T細胞免疫性。(無元件符號說明)
